Convergent Mutations and Single Nucleotide Variants in Mitochondrial Genomes of Modern Humans and Neanderthals.

The genetic contributions of Neanderthals to the modern human genome have been evidenced by the comparison of present-day human genomes with paleogenomes. Neanderthal signatures in extant human genomes are attributed to intercrosses between Neanderthals and archaic anatomically modern humans (AMHs). Although Neanderthal signatures are well documented in the nuclear genome, it has been proposed that there is no contribution of Neanderthal mitochondrial DNA to contemporary human genomes. Here we show that modern human mitochondrial genomes contain 66 potential Neanderthal signatures, or Neanderthal single nucleotide variants (N-SNVs), of which 36 lie in coding regions and 7 result in nonsynonymous changes. Seven N-SNVs are associated with traits such as cycling vomiting syndrome, Alzheimer's disease and Parkinson's disease, and two N-SNVs are associated with intelligence quotient. Based on recombination tests, principal component analysis (PCA) and the complete absence of these N-SNVs in 41 archaic AMH mitogenomes, we conclude that convergent evolution, and not recombination, explains the presence of N-SNVs in present-day human mitogenomes.

Regulatory and governance gaps for human genome editing in Mexico.

Mexico has the in-house technical and regulatory capacity to undertake human genome editing (HGE) governance. However, its regulatory framework must be reformed to be more targeted and govern the application of any emerging HGE technologies, leaving no room for unethical or unsafe practices for reproductive purposes.

Escores de Risco Poligênico: O Próximo Passo para Melhorar a Estratificação de Risco na Doença Arterial Coronariana? / Polygenic Risk Scores: The Next Step for Improved Risk Stratification in Coronary Artery Disease?

Resumo Apesar dos avanços significativos no tratamento da doença arterial coronariana (DAC) e das reduções nas taxas de mortalidade anuais nas últimas décadas, a DAC continua sendo a principal causa de morte no mundo. Consequentemente, há uma necessidade contínua de esforços para abordar essa situação. Os algoritmos clínicos atuais para identificar pacientes em risco são particularmente imprecisos para indivíduos de risco moderado. Por esse motivo, foi sugerido que são necessários testes auxiliares, incluindo triagem genética preditiva. À medida que os estudos genéticos se expandem rapidamente e os dados genômicos se tornam mais acessíveis, diversos escores de risco genético têm sido propostos para identificar e avaliar a suscetibilidade de um indivíduo ao desenvolvimento de doenças, incluindo a DAC. De fato, o campo da genética tem contribuído substancialmente para a previsão de risco, particularmente nos casos em que as crianças têm genitores com DAC prematura, resultando em um risco aumentado de até 75%. Os escores de risco poligênico (PRSs, do inglês polygenic risk scores) surgiram como uma ferramenta potencialmente valiosa para compreender e estratificar o risco genético de um indivíduo. O PRS é calculado como uma soma ponderada de variantes de nucleotídeo único presentes em todo o genoma humano, identificáveis por meio de estudos de associação genômica ampla, e associadas a várias doenças cardiometabólicas. O uso dos PRSs é promissor, pois permite o desenvolvimento de estratégias personalizadas para prevenir ou diagnosticar patologias específicas de forma precoce. Ademais, seu uso é capaz de complementar os escores clínicos existentes, aumentando a precisão da previsão de risco individual. Consequentemente, a aplicação dos PRSs tem o potencial de impactar positivamente os custos e os desfechos adversos associados à DAC. A presente revisão narrativa oferece uma visão ampla do papel dos PRSs no contexto da DAC.

Abstract Despite significant advances in the management of coronary artery disease (CAD) and reductions in annual mortality rates in recent decades, this disease remains the leading cause of death worldwide. Consequently, there is an ongoing need for efforts to address this situation. Current clinical algorithms to identify at-risk patients are particularly inaccurate in moderate-risk individuals. For this reason, the need for ancillary tests has been suggested, including predictive genetic screening. As genetic studies rapidly expand and genomic data becomes more accessible, numerous genetic risk scores have been proposed to identify and evaluate an individual's susceptibility to developing diseases, including CAD. The field of genetics has indeed made substantial contributions to risk prediction, particularly in cases where children have parents with premature CAD, resulting in an increased risk of up to 75%. The polygenic risk scores (PRSs) have emerged as a potentially valuable tool for understanding and stratifying an individual's genetic risk. The PRS is calculated as a weighted sum of single-nucleotide variants present throughout the human genome, identifiable through genome-wide association studies, and associated with various cardiometabolic diseases. The use of PRSs holds promise, as it enables the development of personalized strategies for preventing or diagnosing specific pathologies early. Furthermore, it can complement existing clinical scores, increasing the accuracy of individual risk prediction. Consequently, the application of PRSs has the potential to impact the costs and adverse outcomes associated with CAD positively. This narrative review provides an overview of the role of PRSs in the context of CAD.

Pleiotropic Enhancers are Ubiquitous Regulatory Elements in the Human Genome.

Enhancers are regulatory elements of genomes that determine spatio-temporal patterns of gene expression. The human genome contains a vast number of enhancers, which largely outnumber protein-coding genes. Historically, enhancers have been regarded as highly tissue-specific. However, recent evidence has demonstrated that many enhancers are pleiotropic, with activity in multiple developmental contexts. Yet, the extent and impact of pleiotropy remain largely unexplored. In this study we analyzed active enhancers across human organs based on the analysis of both eRNA transcription (FANTOM5 consortium data sets) and chromatin architecture (ENCODE consortium data sets). We show that pleiotropic enhancers are pervasive in the human genome and that most enhancers active in a particular organ are also active in other organs. In addition, our analysis suggests that the proportion of context-specific enhancers of a given organ is explained, at least in part, by the proportion of context-specific genes in that same organ. The notion that such a high proportion of human enhancers can be pleiotropic suggests that small regions of regulatory DNA contain abundant regulatory information and that these regions evolve under important evolutionary constraints.

Privacidad y confidencialidad de los datos genéticos y genómicos de uso diagnóstico en Colombia. Legislación comparada con Australia / Privacy and Confidentiality of Genetic and Genomic Data for Diagnostic Use in Colombia. Legislation Compared to Australia / Privacidade e confidencialidade de dados genéticos e genômicos para uso diagnóstico na Colômbia. Legislação em comparação com a Austrália

Resumen: La información genética y genómica requiere regulaciones estrictas para su manejo adecuado con el fin de evitar la divulgación inapropiada y la discriminación secundaria, pues tiene una relación directa con los derechos fundamentales y los principios bioéticos. De ahí la necesidad de evaluar la regulación colombiana existente, por lo que se realizó una revisión sistemática de la literatura en bases de datos del 2000 al 2020, sitios web del Congreso de la República de Colombia, la Comisión de Reforma de la Ley Australiana y la Corte Constitucional de Colombia, para identificar las falencias y los aciertos en la jurisprudencia actual del manejo, el control y la accesibilidad de la población colombiana a las pruebas e información genética. Se toma como referente Australia para comprender y plantear mejoras. Se encontró que en Colombia la información genética se cataloga como sensible (Sentencia C-334-10) con regulaciones inespecíficas sin norma legislativa. En contraste, Australia dispone de directrices bioéticas específicas, penalización y protocolos que abarcan las implicaciones individuales y colectivas descritas en el Privacy Legislation Amendment Act del 2006. Es necesario que en Colombia se cree una regulación jurídica específica para la información genética y genómica con énfasis en pautas de uso sobre la privacidad, la divulgación y la no discriminación.

Abstract: Genetic and genomic information requires strict regulations for its proper handling in order to avoid inappropriate disclosure and secondary discrimination, since it is directly related to fundamental rights and bioethical principles. Hence the need to evaluate the existing Colombian regulation, for which a systematic review of the literature was carried out on databases from 2000 to 2020, websites of the Congress of the Republic of Colombia, the Australian Law Reform Commission and the Constitutional Court of Colombia, to identify the shortcomings and the successes in the current jurisprudence of the management, control and accessibility of the Colombian population to tests and genetic information. Australia is taken as a reference to understand and propose improvements. It was found that in Colombia genetic information is classified as sensitive (Sentence C-334-10) with non-specific regulations without legislative norm. In contrast, Australia has specific bioethical guidelines, criminalization and protocols that cover the individual and collective implications described in the Privacy Legislation Amendment Act of 2006. It is necessary that a specific legal regulation be created for genetic and genomic information with emphasis on usage guidelines on privacy, disclosure and non-discrimination in Colombia.

Resumo: As informações genéticas e genômicas requerem regulamentações rígidas para o seu correto manuseio, a fim de evitar a divulgação inadequada e a discriminação secundária, pois está diretamente relacionada aos direitos fundamentais e aos princípios bioéticos. Daí a necessidade de avaliar a regulamentação colombiana existente, para a qual foi realizada uma revisão sistemática da literatura em bancos de dados de 2000 a 2020, sites do Congresso da República da Colômbia, da Comissão Australiana de Reforma da Lei e do Tribunal Constitucional da Colômbia, identificar as deficiências e os sucessos na jurisprudência atual da gestão, controle e acessibilidade da população colombiana a testes e informação genética. A Austrália é tomada como referência para entender e propor melhorias. Constatou-se que na Colômbia a informação genética é classificada como sensível (Sentença C-334-10) com regulamentações não específicas sem norma legislativa. Por outro lado, a Austrália possui diretrizes bioéticas específicas, criminalização e protocolos que abrangem as implicações individuais e coletivas descritas na Lei de Emenda à Legislação de Privacidade de 2006. É necessário que na Colômbia seja criada uma regulamentação legal específica para informações genéticas e genômicas com ênfase no uso diretrizes sobre privacidade, divulgação e não discriminação.

Bases genômicas do carcinoma basocelular não sindrômico: revisão da literatura / Genomic bases of non-syndromic basal cell carcinoma: literature review

RESUMO Introdução: As neoplasias cutâneas não melanoma representam o tipo mais frequente em ambos os sexos no mundo, sendo o carcinoma basocelular o mais prevalente, representando de 75 a 80% dos casos. No Brasil, o número de casos novos esperados para o triênio 2020-2022, será de 83.770 em homens e 93.160 em mulheres, correspondendo a um risco estimado de 80,12 casos novos para 100 mil homens e de 86,65 casos novos para 100 mil mulheres. Este dado demonstra a grande importância do conhecimento genômico na gênese do carcinoma basocelular esporádico. Objetivo: Descrever os principais genes e marcadores moleculares envolvidos na predisposição e na patogênese do carcinoma basocelular não sindrômico. Métodos: Revisão da literatura nas principais bases de dados NCBI-GTR, ClinVar, ClinGen, MedGen, OMIM e GeneReviews , utilizando como descritores: "BCC" e " basal cell carcinoma ". Critérios de inclusão: língua portuguesa ou inglesa, artigos sobre CBC esporádico. Resultados: Foram selecionados treze artigos para análise. A análise revelou uma robusta ligação da via hedgehog na gênese do carcinoma basocelular esporádico, com os principais genes envolvidos representados por PATCH1, PATCH2 e smoothened . As variantes com maior significância clínica foram SMO-M2, PTCH1 e PTCH2-∆22. A mutação mais encontrada fora a relacionada à ação do UVB, sendo representada pela substituição de C>T ou CC>TT no sítio das pirimidinas, tanto no PTCH, quanto no SMO. Conclusão: Extremamente importante aos profissionais que atuam no diagnóstico e tratamento do CBC, dentre os quais os cirurgiões plásticos, pois assim poderão melhor conduzir seus casos, com diagnósticos mais precisos e condutas de prevenção baseadas na suscetibilidade individual de cada paciente, bem como terapêuticas direcionadas e individualizadas com melhores taxas de sucesso.

ABSTRACT Introduction: Non-melanoma skin neoplasms represent the most frequent type in both sexes globally, with basal cell carcinoma being the most prevalent, representing 75 to 80% of cases. In Brazil, the number of new cases expected for the triennium 2020-2022 will be 83,770 in men and 93,160 in women, corresponding to an estimated risk of 80.12 new cases for 100,000 men and 86.65 new cases for 100,000 women. This data demonstrates the great importance of genomic knowledge in the genesis of sporadic basal cell carcinoma. Objective: To describe the main genes and molecular markers involved in the predisposition and pathogenesis of non-syndromic basal cell carcinoma. Methods: Literature review in the main databases NCBI-GTR, ClinVar, ClinGen, MedGen, OMIM and GeneReviews , using as descriptors: "BCC" and " basal cell carcinoma ". Inclusion criteria: Portuguese or EnGLIsh language, articles on sporadic BCC. Results: Thirteen articles were selected for analysis. The analysis revealed a robust hedgehog pathway link in the genesis of sporadic basal cell carcinoma, with the main genes involved represented by PATCH1, PATCH2 and smoothened . The variants with the highest clinical significance were SMO-M2, PTCH1 and PTCH2-∆22. The mutation most found was related to the action of UVB, being represented by the substitution of C>T or CC>TT at the pyrimidine site, both in PTCH and in SMO. Conclusion: Extremely important to professionals working in the diagnosis and treatment of BCC, including plastic surgeons, as this way they can better conduct their cases, with more accurate diagnoses and prevention approaches based on the individual susceptibility of each patient, as well as targeted therapies and individualized with better success rates.

El genoma humano y el desarrollo de la genética forense / The human genome and the development of forensic genetics

El objetivo de este artículo es introducir al médico generalista en los adelantos científicos y técnicos de la genética forense. A partir de los trabajos de Mendel en 1865 sobre hibridación en las plantas se sucedieron avances en el conocimiento del ADN y se incorporaron nuevas técnicas de laboratorio, que permitieron detectar en el ADN un sector no codificante. El conocimiento de este sector junto con los adelantos de informática (software) han permitido progresos innovadores en el desarrollo de las técnicas de identificación forense, logrando que la Genética Forense se convierta en un auxiliar de la justicia para la resolución de casos de filiación, el reconocimiento de restos humanos y el descubrimiento de responsables de crímenes a través de la identificación de ADN encontrado en la escena. (AU)

The objective of this article is to introduce the general practitioner to the scientific and technical advances of forensic genetics. From the work of Mendel in 1865 on hybridization in plants, advances were made in the knowledge of DNA and new laboratory techniques were incorporated, which made it possible to detect a non-coding sector in DNA. Knowledge of this sector together with the advances in computer science (software) have allowed innovative progress in the development of forensic identification techniques, making Forensic Genetics an auxiliary of justice, for the resolution of filiation cases, the recognition of human remains and the discover of the person responsible for the crimes through the identification of their DNA found at the scene of a crime. (AU)

Frequency spectra characterization of noncoding human genomic sequences.

BACKGROUND: Noncoding sequences have been demonstrated to possess regulatory functions. Its classification is challenging because they do not show well-defined nucleotide patterns that can correlate with their biological functions. Genomic signal processing techniques like Fourier transform have been employed to characterize coding and noncoding sequences. This transformation in a systematic whole-genome noncoding library, such as the ENCODE database, can provide evidence of a periodic behaviour in the noncoding sequences that correlates with their regulatory functions. OBJECTIVE: The objective of this study was to classify different noncoding regulatory regions through their frequency spectra. METHODS: We computed machine learning algorithms to classify the noncoding regulatory sequences frequency spectra. RESULTS: The sequences from different regulatory regions, cell lines, and chromosomes possessed distinct frequency spectra, and that machine learning classifiers (such as those of the support vector machine type) could successfully discriminate among regulatory regions, thus correlating the frequency spectra with their biological functions CONCLUSION: Our work supports the idea that there are patterns in the noncoding sequences of the genome.

Reconstructed Lost Native American Populations from Eastern Brazil Are Shaped by Differential Jê/Tupi Ancestry.

After the colonization of the Americas by Europeans and the consequent Trans-Atlantic Slave Trade, most Native American populations in eastern Brazil disappeared or went through an admixture process that configured a population composed of three main genetic components: the European, the sub-Saharan African, and the Native American. The study of the Native American genetic history is challenged by the lack of availability of genome-wide samples from Native American populations, the technical difficulties to develop ancient DNA studies, and the low proportions of the Native American component in the admixed Brazilian populations (on average 7%). We analyzed genome-wide data of 5,825 individuals from three locations of eastern Brazil: Salvador (North-East), Bambui (South-East), and Pelotas (South) and we reconstructed populations that emulate the Native American groups that were living in the 16th century around the sampling locations. This genetic reconstruction was performed after local ancestry analysis of the admixed Brazilian populations, through the rearrangement of the Native American haplotypes into reconstructed individuals with full Native American ancestry (51 reconstructed individuals in Salvador, 45 in Bambui, and 197 in Pelotas). We compared the reconstructed populations with nonadmixed Native American populations from other regions of Brazil through haplotype-based methods. Our results reveal a population structure shaped by the dichotomy of Tupi-/Jê-speaking ancestry related groups. We also show evidence of a decrease of the diversity of nonadmixed Native American groups after the European contact, in contrast with the reconstructed populations, suggesting a reservoir of the Native American genetic diversity within the admixed Brazilian population.

Conocimientos sobre tecnologías ómicas en médicos que inician estudios de especialidad en la atención secundaria / Knowledge about Omic Technologies in Physicians Who Are Starting their Specialty Studies in Secondary Care

Introducción: La introducción de las tecnologías ómicas en la práctica clínica requiere que los profesionales de la salud incorporen conocimientos al respecto. Objetivo: Evaluar los conocimientos sobre tecnologías ómicas de los médicos que inician los estudios de especialidad en el nivel secundario de atención médica. Métodos: Se aplicó un cuestionario a 53 profesionales de la salud, quienes comenzaron sus residencias médicas, tanto clínicas como quirúrgicas, en el Hospital General Docente "Dr. Ernesto Guevara de la Serna" de Las Tunas, Cuba. Se indagó por cuestionario y de forma anónima acerca del conocimiento sobre las pruebas de biología molecular, genéticas y farmacogenéticas, la secuenciación del genoma y las bases de datos de información biológica disponibles en internet. Resultados: El 37,7 por ciento de los participantes no conocía acerca de las pruebas de biología molecular y solo el 3,8 por ciento refirió saber sobre la secuenciación de nueva generación. Aunque el 90,6 por ciento de los interrogados estaban al tanto de alguna prueba genética, ninguno pudo mencionar una correctamente. Solo el 20,8 por ciento declaró su conocimiento de algún gen de susceptibilidad a enfermedades. La posibilidad de secuenciar el genoma completo fue reconocida por el 49,1 por ciento de la muestra. El 90,6 por ciento de los encuestados manifestó interés en recibir información al respecto. Conclusiones: Existe un insuficiente conocimiento sobre las tecnologías ómicas en los participantes en la investigación. Se requiere capacitar a los profesionales de la salud para enfrentar la introducción de la medicina genómica en la práctica clínica, lo que puede y debe hacerse desde la formación médica inicial(AU)

Introduction: The introduction of omic technologies into the clinical practice requires that health professionals incorporate knowledge in this field. Objective: To assess the knowledge about omic technologies of the physicians who are starting their specialty studies in the secondary level of healthcare. Methods: A questionnaire was conducted on 53 health professionals who started their medical residences, both clinical and surgical, at Dr. Ernesto Guevara de la Serna General Teaching Hospital in Las Tunas, Cuba. Both anonymously and by means of the questionnaire, inquiries were made regarding the knowledge about tests in the fields of molecular biology, genetics and pharmacogenetics, about genome sequencing, and about the biological information databases available on the internet. Results: 37.7 percent of the participants did not know about molecular biology tests and only 3.8 percent reported to have some knowledge about next generation sequencing. Although 90.6 percent of the respondents were aware of some genetic test, none could mention one correctly. Only 20.8 percent declared their knowledge about some disease-susceptibility genes. The possibility of sequencing the entire genome was recognized by 49.1 percent of the sample; 90.6 percent of respondents expressed some interest in receiving information about it. Conclusions: There is insufficient knowledge about omic technologies in the research participants. It is required to train health professionals to face the introduction of genomic medicine into the clinical practice, which can and should be done from the beginning ofthe medical training(AU)

Direitos fundamentais, democracia e o Projeto Genoma Humano: bioética e biopolítica / Fundamental rights, democracy and the Human Genome Project: bioethical and biopolitics / Derechos fundamentales, democracia y el Proyecto Genoma Humano: bioética y biopolítica

Resumo Além de importante tecnologia da atualidade, o Projeto Genoma Humano é estrutura política e econômica de produção e reprodução de conceito dominante de saúde. Nessa perspectiva, esta pesquisa discute a garantia da autonomia e liberdade de escolha dos padrões físico-biológicos das atuais e futuras gerações em sociedade na qual esses padrões são historicamente reproduzidos por relações de poder. Para tanto, analisa-se o Projeto Genoma Humano considerando a tensão entre constitucionalismo e democracia, de modo a aproximar aportes da bioética, do biodireito e da biopolítica a partir de perspectiva crítica da sociedade. Como resultado, propõe-se, para reflexão, a institucionalização de audiências públicas baseadas no modelo de democracia deliberativa.

Abstract The Human Genome Project constitutes an important contemporary health technology, but it is also a political and economical structure which of production and reproduction of a dominant concept of health. In this perspective, this research aims to discuss the question of the guarantee of autonomy and freedom of choice of the physical-biological patterns of the future generations, in a society in which those patterns are historically reproduced by power relations. For this reason, a methodology of analysis of the Human Genome Project is used in the context of the tension between constitutionalism and democracy, in order to establish an approximation between the contributions of Bioethics, Biolaw and Biopolitics, in the context of a critical perspective of our society. As a result we propose a reflection about the institutionalisation of public hearings articulated from a model of deliberative democracy.

Resumen El Proyecto Genoma Humano constituye una importante tecnología de salud de la contemporaneidad, pero también una estructura política y económica de producción y reproducción de un concepto dominante de salud. En esa perspectiva, esta investigación tiene como objetivo discutir la cuestión de la garantía de la autonomía y de la libertad de elección de los patrones físicos y biológicos de las futuras generaciones, en una sociedad en la cual estos patrones son históricamente reproducidos por relaciones de poder. Para ello, se utiliza una metodología de análisis del PGH en el ámbito de la tensión entre constitucionalismo y democracia, de modo tal de establecer una aproximación entre los aportes de la Bioética, el Bioderecho y la Biopolítica, en el contexto de una perspectiva crítica de la sociedad. Como resultado, se propone para la reflexión la institucionalización de audiencias públicas articuladas a partir de un modelo de democracia deliberativa.

Genoma humano: aspectos estructurales / Human genome: structural aspects / Genoma humano: aspectos estruturais

El genoma humano, como el de todos los mamíferos y aves, es un mosaico de isocoros, los que son regiones muy largas de ADN (>>100 kb) que son homogéneas en cuanto a su composición de bases. Los isocoros pueden ser divididos en un pequeño número de familias que cubren un amplio rango de niveles de GC (GC es la relación molar de guanina+citosina en el ADN). En el genoma humano encontramos cinco familias, que (yendo de valores bajos a altos de GC) son L1, L2, H1, H2 y H3. Este tipo de organización tiene importantes consecuencias funcionales, tales como la diferente concentración de genes, su regulación, niveles de transcripción, tasas de recombinación, tiempo de replicación, etc. Además, la existencia de los isocoros lleva a las llamadas "correlaciones composicionales", lo que significa que en la medida en que diferentes secuencias están localizadas en diferentes isocoros, todas sus regiones (exones y sus tres posiciones de los codones, intrones, etc.) cambian su contenido en GC, y como consecuencia, cambian tanto el uso de aminoácidos como de codones sinónimos en cada familia de isocoros. Finalmente, discutimos el origen de estas estructuras en un marco evolutivo.

The human genome, as the genome of all mammals and birds, are mosaic of isochores, which are very long streches (>> 100 kb) of DNA that are homogeneous in base composition. Isochores can be divided in a small number of families that cover a broad range of GC levels (GC is the molar ratio of guanine+cytosine in DNA). In the human genome, we find five families, which are (going from GC- poor to GC- rich) L1, L2, H1, H2 and H3. This organization has important consequences, as is the case of the concentration of genes, their regulation, transcription levels, rate of recombination, time of replication, etc. Furthermore, the existence of isochores has as a consequence the so called "compositional correlations", which means that as long as sequences are placed in different families of isochores, all of their regions (exons and their three codon positions, introns, etc.) change their GC content, and as a consequence, both codon and amino acids usage change in each isochore family. Finally, we discuss the origin of isochores within an evolutioary framework.

O genoma humano, como todos os mamíferos e aves, é um mosaico de isocóricas, que são muito longas regiões de ADN (>> 100 kb) que são homogéneos na sua composição de base. Isóquos podem ser divididos em um pequeno número de famílias que cobrem uma ampla gama de níveis de GC (GC é a razão molar de guanina + citosina no DNA). No genoma humano, encontramos cinco famílias, que (variando de valores baixos a altos de GC) são L1, L2, H1, H2 e H3. Este tipo de organização tem importantes conseqüências funcionais, como a diferente concentração de genes, sua regulação, níveis de transcrição, taxas de recombinação, tempo de replicação, etc. Além disso, a existência de isocóricas portada chamado "correlações de composição", o que significa que, na medida em que diferentes sequências estão localizados em diferentes isocóricas, todas as regiões (exs e três posições de codões, intrs, etc.) mudam seu conteúdo em GC e, como consequência, alteram tanto o uso de aminoácidos quanto de códons sinônimos em cada família de isócoros. Finalmente, discutimos a origem dessas estruturas em uma estrutura evolucionária.

CRISPR/Cas9: reflexiones bioéticas sobre las modificacion es genómicas / CRISPR/Cas9: bioethical reflections on genome modifications

CRISPR/Cas9 puede ser considerado el descubrimiento biotecnológico del siglo. Sin embargo, las reflexiones sobre la aceptabilidad y factibilidad de producir cambios permanentes en el ADN de gametos y embriones, ha arrojado nueva luz sobre CRISPR. Por ejemplo al notar que las alteraciones en la línea germinal, pueden ser heredadas y por lo tanto observarse a lo largo de las generaciones. Aunque inicialmente estas transformaciones puedan ser deseables, más allá del impacto tecnológico, la tecnología CRISPR parece tener varias implicancias éticas para la sociedad. Estas pueden ser analizadas a partir de las distintas reacciones que ha despertado CRISPR en todo el mundo. Por ejemplo, en el pedido de suspensión total de la aplicación clínica (es decir, la prohibición de transferir en el útero un embrión previamente modificado con la tecnología CRISPR) hasta tanto no se hayan alcanzado y aprobado ciertos requisitos indispensables para la investigación clínica. En general, esta tecnología ha sido prematuramente caracterizada como "disruptiva". Este texto analizará las implicancias éticas, políticas, sociales, médicas y subjetivas a la luz del fenómeno social - no tecnológico - creado por CRISPR.

CRISPR/Cas9 can be considered the biotechnogical discovery of the century. However, reflections on the plausibility and feasibility of producing permanent changes in the DNA of gametes and embryos throw new light on CRISPR. As in modifications in the germinal line can be inherited and hence, observed throughout generations. While this might be desirable for some, besides the technological impact, CRISPR also seems to have an ethical impact on society. These ethical impacts can be observed in the diverse reactions to CRISPR from across the globe. For instance, a request for the complete suspension of clinical application (that is, the prohibition of implanting an embryo with CRISPR modifications in the uterus) till certain basic research requirements were met and approved. Broadly, this technology has been prematurely also characterized as "disruptive" by some. This paper will analyze these ethical, political, social, medical and subjective reactions in light of the social - not technological - phenomenon created by CRISPR.

Trastorno por atracón, depresión, ansiedad y gen del neuropéptido relacionado con Agouti en pacientes con cirugía bariátrica / Binge eating disorder, depression, anxiety and Agouti gen related neuropeptide in patients with bariatric surgery

Resumen El objetivo de este estudio retroprospectivo fue analizar la relación de la sintomatología de depresión, de ansiedad y el trastorno por atracón (TPA) con el gen del neuropéptido relacionado con Agouti en pacientes sometidos a cirugía bariátrica. Participó una cohorte de 249 adultos (edad media = 41.1, DE =11.3), 64.1% mujeres y 35.9% hombres. La evaluación de la sintomatología depresiva, de ansiedad y de TPA se llevó a cabo a través de una entrevista semiestructurada. Además, se calculó el índice de masa corporal y se tomaron muestras de sangre para realizar un análisis de discriminación alélica. Del total de pacientes, un 20.2% fueron diagnosticados con TPA, encontrando una asociación de este trastorno con una menor pérdida de peso posterior a la cirugía bariátrica a los 6,12, 18 y 24 meses. Las medidas de depresión y de ansiedad no difirieron entre pacientes con TPA vs. sin TPA. Los pacientes con un alelo mutante en el gen del neuropéptido relacionado con Agouti tuvieron un riesgo 2.6 veces mayor de presentar TPA (IC 95% 1.0-6.8; p = 0.04). Además, el TPA parece ser más frecuente en pacientes con el gen del neuropéptido relacionado con Agouti mutado. Destaca la necesidad de que en el estudio de la obesidad se aborden tanto los aspectos psicológicos como los genéticos.

Abstract The objective of this retrospective study was to analyze the relationship between the symptoms of depression, anxiety and binge eating disorder (BED) with the gene related to the Agouti neuropeptide in patients undergoing bariatric surgery. A cohort of 249 adults (average age = 41.1, SD = 11.3), 64.1% women and 35.9% men, were included. The assessment of depression, anxiety and BED symptoms was carried out through a semi-structured interview. In addition, the body mass index was calculated, and blood samples were taken for an allelic discrimination analysis. Of the total number of patients 20.2% were diagnosed with BED, finding an association of this disorder with a lower weight loss after bariatric surgery at 6, 12, 18 and 24 months. The measures of depression and anxiety did not differ between patients with BED vs. without BED. Patients with a mutant allele in the gene related to the Agouti neuropeptide were 2.6 times more likely to present BED (95% C11.0-6.8, P = 0.04). In addition, BED appears to be more frequent in patients with a gene related to the Agouti neuropeptide mutated. When obesity is studied, it is emphasized the need to address both psychological and genetic factors.

Sitio web para diseminar contenidos y recursos sobre las aplicaciones clínicas de las tecnologías ómicas / Website to disseminate contents and resources on the clinical applications of genomic technologies

Introducción: las crecientes aplicaciones clínicas de los avances en el diagnóstico genómico y en el desarrollo de fármacos a partir de la identificación de nuevas dianas moleculares, plantean la necesidad de fomentar competencias relacionadas en los profesionales de salud. Objetivo: diseminar contenidos publicados y recursos disponibles en un sitio web sobre las aplicaciones actuales o potenciales de la genómica en la práctica clínica, de utilidad en la docencia, la asistencia y la investigación. Métodos: a partir de la plataforma de blogs de Infomed se construyó un sitio web configurado con una página principal y tres bloques: noticias, créditos y recursos de información. Se incluyeron cinco páginas adicionales: inmunoinformática, otros proyectos genoma, eventos, libros y otros recursos. Se diseñaron estrategias de gestión de información científica para sostener su actualización permanente. Resultados: la relación de notas publicadas abarca diversas categorías como bases de datos, bioinformática, cáncer, capacitación, diagnóstico, farmacogenómica, medicina personalizada y tratamientos, entre otras. Se proporciona acceso a universidades, otras instituciones, bases de datos, revistas científicas, así como a libros o capítulos sobre la temática. Conclusiones: el sitio web Medicina Genómica ha sido diseñado como colección de recursos que incremente los niveles de conocimientos, despierte el interés y genere acciones para la promoción de los avances de la genómica en la práctica clínica(AU)

Introduction: The growing number in the clinical applications of genomic diagnosis advances and drug development from the identification of new molecular targets raise the need to promote related competencies in health professionals. Objective: To disseminate published contents and resources available on a website about current or potential applications of genomics in clinical practice, useful in teaching, assistance and research. Methods: From the blog platform of Infomed, a web site was constructed and configured with a main page and three blocks: news, credits and information resources. Five additional pages were included: immunoinformatics, other genome projects, events, books, and other resources. Scientific information management strategies were designed to support its ongoing updating. Results: The list of published notes covers diverse categories such as databases, bioinformatics, cancer, capacity building, diagnosis, pharmacogenomics, personalized medicine and treatments, among others. It provides access to universities, other institutions, databases, scientific journals, as well as books or chapters on the subject. Conclusions: The website on Genomic Medicine has been designed as a gathering of resources that increase knowledge levels, arouse interest and generate actions to promote the advances of genomics in clinical practice(AU)

Condicionada a seleção artificial: eliminar os mais fracos ou homogeneizar a "raça"? / Condicionada la selección artificial: ¿eliminar los más débiles o homogeneizar la "raza"? / Conditioned to Artificial Selection: Eliminate the Weakest or Homogenize the "Race"?

Resumo O controle populacional mediante práticas discriminatórias é encontrado em todos os momentos históricos. Nunca antes, todavia, o emprego das ciências (naturais e humanas) esteve tão próximo de alcançar a criação de novos mecanismos geradores de "subespécies" humanas. Esta pesquisa trata, fundamentada em referencial teórico selecionado, dos desafios biotecnológicos e bioéticos na senda das manipulações quanto ao desenvolvimento de práticas eventualmente nocivas no contexto pluralista. A segregação ou, até mesmo, a destruição dos seres humanos indesejáveis é temível reflexo duma sociedade egocêntrica e, em grande medida, preconceituosa. Porém, o futuro não será, necessariamente, obscuro se o Homo sapiens souber agir ética e positivamente.

Resumen El control de la población mediante prácticas discriminatorias se encuentra en todos los momentos históricos. Sin embargo, el empleo de las ciencias (naturales y humanas) nunca había estado tan cerca de alcanzar la creación de nuevos mecanismos generadores de "subespecies" humanas. La investigación trata, fundamentada en un marco teórico seleccionado, los retos biotecnológicos y bioéticos en la senda de las manipulaciones en cuanto al desarrollo de prácticas eventualmente nocivas en el contexto pluralista. La segregación o, incluso, la destrucción de los seres humanos indeseables es temible reflejo de una sociedad egocéntrica y, en gran medida, prejuiciosa. No obstante, el futuro no será, necesariamente, oscuro si el Homo sapiens sabe actuar ética y positivamente.

Abstract Population control through discriminatory practices is found at all times in history. Never before, however, has use of the sciences (natural and human) been so close to achieving the creation of new mechanisms for generating human "subspecies". This study, which is based on a selected theoretical framework, deals with the biotechnological and bioethical challenges on the path to manipulation as concerns the development of potentially harmful practices in a pluralist context. Segregation or even the destruction of undesirable human beings is a frightening reflection of an egocentric and largely prejudiced society. However, the future will not necessarily be obscure if Homo sapiens can act ethically and positively.

Mapping of microRNAs related to cervical cancer in Latin American human genomic variants.

Background: MicroRNAs are related to human cancers, including cervical cancer (CC) caused by HPV. In 2018, approximately 56.075 cases and 28.252 deaths from this cancer were registered in Latin America and the Caribbean according to GLOBOCAN reports. The main molecular mechanism of HPV in CC is related to integration of viral DNA into the hosts' genome. However, the different variants in the human genome can result in different integration mechanisms, specifically involving microRNAs (miRNAs). Methods: The miRNAs associated with CC were obtained from literature, the miRNA sequences and four human genome variants (HGV) from Latin American populations were obtained from miRBase and 1000 Genomes Browser, respectively. HPV integration sites near cell cycle regulatory genes were identified. miRNAs were mapped on HGV. miRSNPs were identified in the miRNA sequences located at HPV integration sites on the Latin American HGV.  Results: Two hundred seventy-two miRNAs associated with CC were identified in 139 reports from different geographic locations. By mapping with Blast-Like Alignment Tool (BLAT), 2028 binding sites were identified from these miRNAs on the human genome (version GRCh38/hg38); 42 miRNAs were located on unique integration sites; and miR-5095, miR-548c-5p and miR-548d-5p were involved with multiple genes related to the cell cycle. Thirty-seven miRNAs were mapped on the Latin American HGV (PUR, MXL, CLM and PEL), but only miR-11-3p, miR-31-3p, miR-107, miR-133a-3p, miR-133a-5p, miR-133b, miR-215-5p, miR-491-3p, miR-548d-5p and miR-944 were conserved. Conclusions: Ten miRNAs were conserved in the four HGV. In the remaining 27 miRNAs, substitutions, deletions or insertions were observed. These variation patterns can imply differentiated mechanisms towards each genomic variant in human populations because of specific genomic patterns and geographic features. These findings may help in determining susceptibility for CC development. Further identification of cellular genes and signalling pathways involved in CC progression could lead new therapeutic strategies based on miRNAs.

Chocó, Colombia: a hotspot of human biodiversity.

OBJECTIVE: Chocó is a state located on the Pacific coast of Colombia that has a majority Afro-Colombian population. The objective of this study was to characterize the genetic ancestry, admixture and diversity of the population of Chocó, Colombia. METHODOLOGY: Genetic variation was characterized for a sample of 101 donors (61 female and 40 male) from the state of Chocó. Genotypes were determined for each individual via the characterization of 610,545 single nucleotide polymorphisms genome-wide. Haplotypes for the uniparental mitochondrial DNA (female) and Y-DNA (male) chromosomes were also determined. These data were used for comparative analyses with a number of worldwide populations, including putative ancestral populations from Africa, the Americas and Europe, along with several admixed American populations. RESULTS: The population of Chocó has predominantly African genetic ancestry (75.8%) with approximately equal parts European (13.4%) and Native American (11.1%) ancestry. Chocó shows relatively high levels of three-way genetic admixture, and far higher levels of Native American ancestry, compared to other New World African populations from the Caribbean and the United States. There is a striking pattern of sex-specific ancestry in Chocó, with Native American admixture along the female lineage and European admixture along the male lineage. The population of Chocó is also characterized by relatively high levels of overall genetic diversity compared to both putative ancestral populations and other admixed American populations. CONCLUSION: These results suggest a unique genetic heritage for the population of Chocó and underscore the profound human genetic diversity that can be found in the region.

A decade of human genome project conclusion: Scientific diffusion about our genome knowledge.

The Human Genome Project (HGP) was initiated in 1990 and completed in 2003. It aimed to sequence the whole human genome. Although it represented an advance in understanding the human genome and its complexity, many questions remained unanswered. Other projects were launched in order to unravel the mysteries of our genome, including the ENCyclopedia of DNA Elements (ENCODE). This review aims to analyze the evolution of scientific knowledge related to both the HGP and ENCODE projects. Data were retrieved from scientific articles published in 1990-2014, a period comprising the development and the 10 years following the HGP completion. The fact that only 20,000 genes are protein and RNA-coding is one of the most striking HGP results. A new concept about the organization of genome arose. The ENCODE project was initiated in 2003 and targeted to map the functional elements of the human genome. This project revealed that the human genome is pervasively transcribed. Therefore, it was determined that a large part of the non-protein coding regions are functional. Finally, a more sophisticated view of chromatin structure emerged. The mechanistic functioning of the genome has been redrafted, revealing a much more complex picture. Besides, a gene-centric conception of the organism has to be reviewed. A number of criticisms have emerged against the ENCODE project approaches, raising the question of whether non-conserved but biochemically active regions are truly functional. Thus, HGP and ENCODE projects accomplished a great map of the human genome, but the data generated still requires further in depth analysis. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:215-223, 2016.